The Emergence of the New P.4 Lineage of SARS-CoV-2 With Spike L452R Mutation in Brazil.

The emergence of several SARS-CoV-2 lineages presenting adaptive mutations is a matter of concern worldwide due to their potential ability to increase transmission and/or evade the immune response. While performing epidemiological and genomic surveillance of SARS-CoV-2 in samples from Porto Ferreira-São Paulo-Brazil, we identified sequences classified by pangolin as B.1.1.28 harboring Spike L452R mutation, in the RBD region. Phylogenetic analysis revealed that these sequences grouped into a monophyletic branch, with others from Brazil, mainly from the state of São Paulo. The sequences had a set of 15 clade defining amino acid mutations, of which six were in the Spike protein. A new lineage was proposed to Pango and it was accepted and designated P.4. In samples from the city of Porto Ferreira, P.4 lineage has been increasing in frequency since it was first detected in March 2021, corresponding to 34.7% of the samples sequenced in June, the second in prevalence after P.1. Also, it is circulating in 30 cities from the state of São Paulo, and it was also detected in one sample from the state of Sergipe and two from the state of Rio de Janeiro. Further studies are needed to understand whether P.4 should be considered a new threat.

Presentation of fatal stroke due to SARS-CoV-2 and dengue virus coinfection.

Herein, we report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and dengue coinfection, presented as a fatal stroke in our hospital, in São José do Rio Preto, São Paulo State, a Brazilian city hyperendemic for dengue viruses and other arthropod-borne viruses (arboviruses) and currently facing a surge of SARS-CoV-2 cases. This case is the first described in the literature and contributes to the better understanding of clinical presentations of two important diseases in a tropical setting.

Immunopathological mechanisms involved in SARS-CoV-2 infection

ABSTRACT Introduction: Coronavirus disease 2019 (Covid-19) has become a global health emergency. Although many scientific advances have been achieved over the last few months, the knowledge about how the etiologic agent SARS-CoV-2 interacts with the host's immune system, regulating the pathogenesis and the outcome of the disease, is not yet fully understood. Objective: This is a narrative literature review to discuss the available evidence on modes of transmission and the main immunopathological mechanisms involved in SARS-CoV-2 infection. Material and method: A search in the indexed journals was carried out in the PubMed/MEDLINE database, during the period from January to May 2020. The following descriptors were used in the research: Covid-19, SARS-CoV-2, transmission, immunity, immunopathogenesis, and pathogenesis. Results and discussion: Transmission of SARS-CoV-2 occurs through contact with airway secretions from a symptomatic patient. However, scientific evidence encourages transmission by asymptomatic and/or oligosymptomatic patients. Immunopathological studies suggest that the hypercytokinaemia promotes lung tissue damage and, subsequently, organ and system involvement, leading to decompensation, organ dysfunction and death. Regarding the humoral response, the high titers of B lymphocytes and antibodies, traditionally, correlated with the protection of the host, may be associated with the severity of the disease by SARS-CoV-2. Conclusion: The host's immune response is determinant in the pathogenesis of Covid-19. However, further in vivo and/or in vitro studies are needed to elucidate the pathogenic mechanisms of SARS-CoV-2 and, thus, assist in the development of a vaccine and/or therapeutic target. RESUMEN Introducción: La enfermedad por coronavirus 2019 (Covid-2019) se ha convertido en una emergencia sanitaria mundial. A pesar de los muchos avances científicos recientes, el conocimiento acerca de cómo el agente etiológico SARS-CoV-2 interactúa con el sistema inmunitario del huésped, regulando la patogénesis y el resultado de la enfermedad, todavía no está totalmente claro. Objetivo: Revisión de la literatura a fin de discutir la evidencia disponible sobre las formas de transmisión y los principales mecanismos inmunopatológicos involucrados en la infección por SARS-CoV-2. Material y métodos: Se realizó una búsqueda por periódicos indexados en la base de datos PubMed/MEDLINE, desde enero hasta mayo de 2020. Se han utilizado las siguientes palabras clave en la investigación: Covid-19, SARS-CoV-2, transmission, immunity, immunopathogenesis y pathogenesis. Resultados y discusión: La transmisión del SARS-CoV-2 ocurre por el contacto con secreciones de las vías respiratorias de un paciente sintomático. Sin embargo, evidencias científicas indican la transmisión por pacientes asintomáticos y/o oligosintomáticos. Estudios inmunopatológicos sugieren que la tormenta de citocinas causa lesión en pulmones y, posteriormente, daño en órganos y sistemas, que conduce a la descompensación, disfunción orgánica y muerte. Sobre la inmunidad humoral, los títulos elevados de linfocitos B y anticuerpos, tradicionalmente relacionados con la protección del huésped, pueden estar asociados a la gravedad de la enfermedad por SARS-CoV-2. Conclusión: La respuesta inmunológica del huésped es determinante para la patogénesis de la Covid-19. No obstante, se necesitan más estudios in vivo y/o in vitro para aclarar los mecanismos de patogenicidad del SARS-CoV-2 y, así, ayudar en el desarrollo de una vacuna y/u objetivo terapéutico. RESUMO Introdução: A doença do coronavírus 2019 (Covid-19) tornou-se uma emergência de saúde mundial. Embora muitos avanços científicos tenham sido alcançados nos últimos meses, o conhecimento sobre como o agente etiológico SARS-CoV-2 interage com o sistema imunológico do hospedeiro, regulando a patogênese e o resultado da doença, ainda não está totalmente esclarecido. Objetivo: Revisão da literatura com o objetivo de discutir as evidências disponíveis sobre as formas de transmissão e os principais mecanismos imunopatológicos envolvidos na infecção pelo SARS-CoV-2. Material e método: Realizou-se uma busca de periódicos indexados na base de dados PubMed/MEDLINE, durante o período de janeiro a maio de 2020. Os seguintes descritores foram utilizados na pesquisa: Covid-19, SARS-CoV-2, transmission, immunity, immunnopathogenesis e pathogenesis. Resultados e discussão: A transmissão do SARS-CoV-2 ocorre pelo contato com secreções das vias aéreas de um paciente sintomático. No entanto, evidências científicas fomentam a transmissão por pacientes assintomáticos e/ou oligossintomáticos. Os estudos imunopatológicos sugerem que a hipercitocinemia promove lesão do tecido pulmonar e, posteriormente, comprometimento de órgãos e sistemas, levando a descompensação, disfunção orgânica e óbito. Sobre a resposta humoral, os altos títulos de linfócitos B e anticorpos, tradicionalmente correlacionados com a proteção do hospedeiro, podem estar associados à gravidade da doença pelo SARS-CoV-2. Conclusão: A resposta imunológica do hospedeiro é determinante na patogênese da Covid-19. No entanto, mais estudos in vivo e/ou in vitro são necessários para elucidar os mecanismos de patogenicidade do SARS-CoV-2 e, assim, auxiliar no desenvolvimento de uma vacina e/ou alvo terapêutico.

Immunopathological mechanisms involved in SARS-CoV-2 infection

ABSTRACT Introduction: Coronavirus disease 2019 (Covid-19) has become a global health emergency. Although many scientific advances have been achieved over the last few months, the knowledge about how the etiologic agent SARS-CoV-2 interacts with the host's immune system, regulating the pathogenesis and the outcome of the disease, is not yet fully understood. Objective: This is a narrative literature review to discuss the available evidence on modes of transmission and the main immunopathological mechanisms involved in SARS-CoV-2 infection. Material and method: A search in the indexed journals was carried out in the PubMed/MEDLINE database, during the period from January to May 2020. The following descriptors were used in the research: Covid-19, SARS-CoV-2, transmission, immunity, immunopathogenesis, and pathogenesis. Results and discussion: Transmission of SARS-CoV-2 occurs through contact with airway secretions from a symptomatic patient. However, scientific evidence encourages transmission by asymptomatic and/or oligosymptomatic patients. Immunopathological studies suggest that the hypercytokinaemia promotes lung tissue damage and, subsequently, organ and system involvement, leading to decompensation, organ dysfunction and death. Regarding the humoral response, the high titers of B lymphocytes and antibodies, traditionally, correlated with the protection of the host, may be associated with the severity of the disease by SARS-CoV-2. Conclusion: The host's immune response is determinant in the pathogenesis of Covid-19. However, further in vivo and/or in vitro studies are needed to elucidate the pathogenic mechanisms of SARS-CoV-2 and, thus, assist in the development of a vaccine and/or therapeutic target.